Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

Steve Horvath, Abu Nasir Mohammad Nazmul Hossain, Rodney P.E. Pollard, Frans G.M. Kroese, Arjan Vissink, Cees G.M. Kallenberg, Fred K.L. Spijkervet, Hendrika Bootsma, Sara A. Michie, Sven U. Gorr, Ammon B. Peck, Chaochao Cai, Hui Zhou, David T.W. Wong

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Introduction: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice.Methods: Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways.Results: Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation.Conclusion: Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.

Original languageEnglish (US)
Article numberR238
JournalArthritis Research and Therapy
Volume14
Issue number6
DOIs
StatePublished - Nov 1 2012

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Systems Analysis
Salivary Glands
Systems Biology
Sjogren's Syndrome
Inbred NOD Mouse
Germinal Center
Gene Regulatory Networks
Parotid Gland
Genes
Autoimmune Diseases
Leukocytes
Chronic Disease
Down-Regulation
Software
Genome
RNA
Gene Expression

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model. / Horvath, Steve; Nazmul Hossain, Abu Nasir Mohammad; Pollard, Rodney P.E.; Kroese, Frans G.M.; Vissink, Arjan; Kallenberg, Cees G.M.; Spijkervet, Fred K.L.; Bootsma, Hendrika; Michie, Sara A.; Gorr, Sven U.; Peck, Ammon B.; Cai, Chaochao; Zhou, Hui; Wong, David T.W.

In: Arthritis Research and Therapy, Vol. 14, No. 6, R238, 01.11.2012.

Research output: Contribution to journalArticle

Horvath, S, Nazmul Hossain, ANM, Pollard, RPE, Kroese, FGM, Vissink, A, Kallenberg, CGM, Spijkervet, FKL, Bootsma, H, Michie, SA, Gorr, SU, Peck, AB, Cai, C, Zhou, H & Wong, DTW 2012, 'Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model', Arthritis Research and Therapy, vol. 14, no. 6, R238. https://doi.org/10.1186/ar4081
Horvath, Steve ; Nazmul Hossain, Abu Nasir Mohammad ; Pollard, Rodney P.E. ; Kroese, Frans G.M. ; Vissink, Arjan ; Kallenberg, Cees G.M. ; Spijkervet, Fred K.L. ; Bootsma, Hendrika ; Michie, Sara A. ; Gorr, Sven U. ; Peck, Ammon B. ; Cai, Chaochao ; Zhou, Hui ; Wong, David T.W. / Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model. In: Arthritis Research and Therapy. 2012 ; Vol. 14, No. 6.
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abstract = "Introduction: Primary Sj{\"o}gren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice.Methods: Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways.Results: Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation.Conclusion: Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.",
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AU - Horvath, Steve

AU - Nazmul Hossain, Abu Nasir Mohammad

AU - Pollard, Rodney P.E.

AU - Kroese, Frans G.M.

AU - Vissink, Arjan

AU - Kallenberg, Cees G.M.

AU - Spijkervet, Fred K.L.

AU - Bootsma, Hendrika

AU - Michie, Sara A.

AU - Gorr, Sven U.

AU - Peck, Ammon B.

AU - Cai, Chaochao

AU - Zhou, Hui

AU - Wong, David T.W.

PY - 2012/11/1

Y1 - 2012/11/1

N2 - Introduction: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice.Methods: Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways.Results: Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation.Conclusion: Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.

AB - Introduction: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice.Methods: Parotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL/6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways.Results: Nineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation.Conclusion: Our systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.

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